Osman Eiman A, Rynes Thomas P, Wang Y Lucia, Mruk Karen, McKeague Maureen
Department of Chemistry, Faculty of Science, McGill University Montreal QC H3A 0B8 Canada
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University Greenville NC 27834 USA.
Chem Sci. 2024 Feb 19;15(13):4770-4778. doi: 10.1039/d3sc05735f. eCollection 2024 Mar 27.
We report a genetically encoded aptamer biosensor platform for non-invasive measurement of drug distribution in cells and animals. We combined the high specificity of aptamer molecular recognition with the easy-to-detect properties of fluorescent proteins. We generated six encoded aptasensors, showcasing the platform versatility. The biosensors display high sensitivity and specificity for detecting their specific drug target over related analogs. We show dose dependent response of biosensor performance reaching saturating drug uptake levels in individual live cells. We designed our platform for integration into animal genomes; thus, we incorporated aptamer biosensors into zebrafish, an important model vertebrate. The biosensors enabled non-invasive drug biodistribution imaging in whole animals across different timepoints. To our knowledge, this is the first example of an aptamer biosensor-expressing transgenic vertebrate that is carried through generations. As such, our encoded platform addresses the need for non-invasive whole animal biosensing ideal for pharmacokinetic-pharmacodynamic analyses that can be expanded to other organisms and to detect diverse molecules of interest.
我们报道了一种用于非侵入性测量细胞和动物体内药物分布的基因编码适配体生物传感器平台。我们将适配体分子识别的高特异性与荧光蛋白易于检测的特性相结合。我们生成了六种编码适配体传感器，展示了该平台的多功能性。这些生物传感器对检测其特定药物靶点相对于相关类似物具有高灵敏度和特异性。我们展示了生物传感器性能的剂量依赖性响应，在单个活细胞中达到饱和药物摄取水平。我们将我们的平台设计用于整合到动物基因组中；因此，我们将适配体生物传感器整合到斑马鱼（一种重要的模式脊椎动物）中。这些生物传感器能够在整个动物的不同时间点进行非侵入性药物生物分布成像。据我们所知，这是首个表达适配体生物传感器的转基因脊椎动物传代的例子。因此，我们的编码平台满足了对非侵入性全动物生物传感的需求，这对于药代动力学 - 药效学分析是理想的，并且可以扩展到其他生物体以及检测各种感兴趣的分子。
